Prospective clinical trial of Intravitreal aflibercept treatment for PolypoIdal choroidal vasculopathy with hemorrhage or exudation (EPIC study): 6 month results

Abstract

Background: Polypoidal choroidal vasculopathy is a variant of choroidal neovascularization and neovascular age related macular degeneration presenting with hemorrhagic and exudative changes within the macula and/or peripapillary region leading to vision loss. In contrast to neovascular age related macular degeneration, polypoidal choroidal vasculopathy has differing clinical manifestations and treatment strategies. Historically, polypoidal choroidal vasculopathy complexes are less responsive to anti-vascular endothelial growth factor therapy with no prospective clinical trials evaluating aflibercept in management of polypoidal choroidal vasculopathy. Herein we prospectively evaluate the efficacy and safety of intravitreal aflibercept in polypoidal choroidal vasculopathy.

Methods: A prospective, open-label, investigator-sponsored trial of intravitreal aflibercept for polypoidal choroidal vasculopathy in 21 eyes was conducted. Injections were administered monthly for 3 initial treatments, then every other month with monthly evaluations. The primary outcome measures were the mean change in best corrected visual acuity and adverse events. Secondary outcome measures included stabilization of vision, presence of subretinal hemorrhage, serous detachment, retinal pigment epithelial detachment, and regression of polypoidal complexes on indocyanine green angiography.

Results: At 6 months, the median visual acuity was 20/40 (range 20/25-20/200) with a mean Early Treatment Diabetic Retinopathy Study vision of 68.4 letters. There was a gain of 2.76 Early Treatment Diabetic Retinopathy Study letters at 6 months (p = 0.15). No patient developed severe vision loss (≤15 letters) and vision was stable or improved in 19/21 eyes (91 %). Subretinal fluid resolved in 13/18 eyes (72 %), and subretinal hemorrhage resolved in 6/8 eyes (75 %) respectively. The polyps regressed in 14/21 eyes (67 %) and the branching vascular network decreased in 1 eye and was stable in all other eyes. The retinal pigment epithelial detachment improved in 13/15 eyes (87 %). Bimonthly treatment occurred in 15/21 patients (71 %). There were no adverse events.

Conclusions: Intravitreal aflibercept results in stabilization of vision, resolution of exudative and hemorrhagic complications with regression of polyps in polypoidal choroidal vasculopathy. Eyes with polypoidal choroidal vasculopathy previously treated with ranibizumab and bevacizumab can show marked improvement in the retinal pigment epithelial detachments and persistent polyps with aflibercept therapy.

Trial registration: Clinical trials.gov NCT01871376 , June 4(th) 2013.

Keywords: Aflibercept; Choroidal neovascularization; Exudative macular degeneration; Polypoidal choroidal vasculopathy; Retinal pigment epithelial detachment.

Figures

Fig. 1

Marked reduction of treatment-naïve polyp after 6 months of intravitreal aflibercept. a. EPIC study baseline ICG angiogram (left) with correlated OCT study (right). Note the hyperfluorescent polyp with hypofluorescent ring on ICG angiogram. On the OCT, an inverted U-shaped polyp (arrow) is seen with surrounding serous detachment. b. ICG angiogram (left) following 6 months of intravitreal aflibercept with corresponding OCT (right) reveals marked reduction in the polyp (arrow)

Fig. 2

ICG angiogram with correlated OCT study in a previously treated eye in the PEARL 2 Study (12 2.0 mg ranibizumab + 12 1.0 mg ranibizumab) with additional bevacizumab intravitreal injections prior to entry into the EPIC study. a. Baseline EPIC Study images. ICG angiogram shows hypofluorescence (see arrowhead) in the area of the subretinal hyperreflective material and the central RPED. OCT shows a central RPED (arrow) with nasal subretinal hyperreflective material (asterisk). b. EPIC Month 6 imaging. ICG angiogram shows decrease in the area of hypofluorescence. OCT shows resolution of the subretinal hyperreflective material and decrease in the RPED. Visual acuity improved from 20/160 to 20/63 (+30 letters)

Fig. 3

Resolution of a vascularized RPED after aflibercept therapy. a. An Asian male with a persistent large vascularized RPED after 24 months of high dose ranibizumab therapy (12 2.0 mg ranibizumab + 12 1.0 mg ranibizumab injections) in PEARL2 study at EPIC baseline (upper left). Resolution of the vascularized RPED which initially resolved at month 3 and stayed resolved at month 6 (upper right) b. Treatment naïve Caucasian female with vascularized RPED at EPIC baseline (left) and after aflibercept therapy at month 6 (right). Note the marked improvement in the vascularized RPED. c. Corresponding ICG angiogram to patient in B. Increased visibility of BVN after RPED resolution on aflibercept therapy. ICG angiogram shows hypofluorescence in the area of the RPED at baseline with inferior PCV complex (left). Follow-up ICG angiogram shows decreased hypofluorescence due to resolution of the RPED. Note the increased visibility of the hyperfluorescent BVN (right)

Fig. 4

Resolution of polyps on aflibercept in an Asian Male with a large vascular PCV complex persisting after 24 months of high dose ranibizumab therapy (PEARL2, 6 2.0 mg ranibizumab + 18 1.0 mg ranibizumab injections). a. EPIC baseline ICG angiogram showing persistent polyps (circles). b-d. EPIC baseline images with ICG angiogram and corresponding polyps (arrows) on OCT. e. Epic month 6 ICG angiogram showing marked polyp resolution. f-h. EPIC month 6 ICG angiogram with corresponding OCT images displaying significant polyp (arrows) reduction on aflibercept therapy